An antibody sees one thing. A T cell receptor always sees two — a fragment, and the plate holding it.
Immunology has one picture it draws more than any other: an antibody
clamping onto the surface of a virus. Lock and key. One thing recognises
one thing.
A T cell receptor is not built that way.
What a TCR sees is fragment + plate — the two stuck together as one
The fragment is a peptide: an 8-to-20 letter scrap left over when a
protein is broken up inside a cell. The plate is HLA, which is what we
call human MHC. The two together are written pMHC.
This course stays on that meeting place and nothing else.
1974 — a result nobody expected
Rolf Zinkernagel and Peter Doherty were running a simple experiment. Infect
a mouse with a virus, pull out its cytotoxic T cells, mix them with
virus-infected cells, and see whether the cells get killed.
They did. So far, so expected.
The control is where it went strange. Those cells were infected with
the same virus — but taken from a different mouse strain.
Same strain · infected
killed
Different strain · infected
not killed
Same strain · not infected
not killed
The virus is the same. Same antigen, no killing. Which means a T cell
is not looking at the antigen alone. It also looks at the plate of the house
that is holding it.
This is called MHC restriction. The two of them took the 1996 Nobel
Prize in Physiology or Medicine for it.
VDJdb 2026-06-03. One row is one chain — TRA or TRB.
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GILGFVFTL from influenza M1 — the single most studied fragment in immunology.
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Take the fragment and the plate apart. Neither one alone moves a T cell.
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Where this course sits
This site already has courses on T cells and on antigen presentation. The
work is divided so they do not overlap.
Course
Its job
/tcell T cell receptors and the repertoire
How the receptor is built — V(D)J, CDR3, diversity
/antigen Antigen presentation and neoantigens
How the fragment gets onto the plate — proteasome, TAP, binding motifs
This course
Where the two meet — docking, polymorphism, CD4/CD8, dwell time
Order does not matter. But if you already know CDR3 from /tcell
and the groove from /antigen, everything from lesson 3 onward reads
a great deal faster.
🤔 Check yourself
In Zinkernagel and Doherty's experiment, why were infected cells from a different mouse strain not killed?
Answer The antigen was identical. The only thing that differed was the plate. That is how we learned a T cell sees pMHC as one object.
🤔 Check yourself
What is the biggest difference between an antibody and a TCR?
Answer An antibody grabs free-floating antigen as it is. A TCR can only see a fragment loaded onto a plate on a cell surface.
🤔 Check yourself
Which of these does this course not cover?
Answer V(D)J recombination belongs to /tcell, lessons 2 and 6. Here we only ask what an already-built receptor sees, and how.
